Abstract
The intrinsically disordered tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and other human tauopathies. Abnormal post-translational modifications of tau, such as truncation, are causally involved in the onset/development of these neurodegenerative diseases. In this context, the AD-relevant N-terminal fragment mapping between 26 and 44 amino acids of protein (tau26-44) is interesting, being endowed with potent neurotoxic effects in vitro and in vivo. However, the understanding of the mechanism(s) of tau26-44 toxicity is a challenging task because, similarly to the full-length tau, it does not have a unique 3D structure but exists as dynamic ensemble of conformations. Here we use Atomic Force Spectroscopy, Small Angle X-ray Scattering and Molecular Dynamics simulation to gather structural and functional information on the tau26-44. We highlight the presence, the type and the location of its temporary secondary structures and we unveil the occurrence of relevant transient tertiary conformations that could contribute to tau26-44 toxicity. Data are compared with those obtained on the biologically-inactive, reverse-sequence (tau44-26 peptide) which has the same mass, charge, aminoacidic composition as well as the same overall unfolded character of tau26-44.
Lingua originale | English |
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pagine (da-a) | 278-289 |
Numero di pagine | 12 |
Rivista | International Journal of Biological Macromolecules |
Volume | 141 |
DOI | |
Stato di pubblicazione | Pubblicato - 2019 |
Keywords
- Alzheimer Disease
- Alzheimer's disease (AD)
- Amino Acid Sequence
- Animals
- Atomic Force Microscopy (AFM)
- Humans
- Microscopy, Atomic Force
- Molecular Dynamics (MD) simulation
- Molecular Dynamics Simulation
- Neurons
- Peptides
- Protein Conformation
- Rats
- Small Angle X-ray Scattering (SAXS)
- Structure-Activity Relationship
- Tau protein
- Tauopathies
- X-Ray Diffraction
- tau Proteins